Reduced human platelet uptake by pig livers deficient in the asialoglycoprotein receptor 1 protein

BACKGROUND: The lethal thrombocytopenia that accompanies liver xenotransplantation is a barrier to clinical application. Human platelets are bound by the asialoglycoprotein receptor (ASGR) on pig sinusoidal endothelial cells and phagocytosed. Inactivation of the ASGR1 gene in donor pigs may prevent xenotransplantation-induced thrombocytopenia. METHODS: Transcription activator-like effector nucleases (TALENs) were targeted to the ASGR1 gene in pig liver-derived cells. ASGR1 deficient pig cells were used for somatic cell nuclear transfer (SCNT). ASGR1 knock out (ASGR1-/-) fetal fibroblasts were used to produce healthy ASGR1 knock out piglets. Human platelet uptake was measured in ASGR1+/+ and ASGR1-/- livers. RESULTS: Targeted disruption of the ASGR1 gene with TALENs eliminated expression of the receptor. ASGR1-/- livers phagocytosed fewer human platelets than domestic porcine livers during perfusion. CONCLUSIONS: The use of TALENs in liver-derived cells followed by SCNT enabled the production of healthy homozygous ASGR1 knock out pigs. Livers from ASGR1-/- pigs exhibit decreased human platelet uptake. Deletion of the ASGR1 gene is a viable strategy to diminish platelet destruction in pig-to-human xenotransplantation

CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells

The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total HIV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA–positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART

Effect of THI, NDF and rumination in milk production by Holstein cows

Objective: The aim of the present study was to evaluate the effect of the THI, NDF and rumination rate (RR) on milk production in Holstein cows in a dairy farm located in Bajío de San José, Jalisco Design/methodology/approach: The temperature-humidity index (THI) is an indicator of the effect of the environmental climate can have on milk production, likewise nutritional content of forage is affected by weather conditions, as the neutral detergent fiber (NDF) is related with rumination activity of cows, increasing THI has shown a direct effect on milk production in cows. HealthyCow 24 ® CSR was used (SCR Engineers Ltd., Netanya, Israel), to monitor rumination, from a total record of 284 cows with 2, 3, and 4 lactacion through august to december 2020 period, analysing NDF content from total mixed ration and monitoring THI. Results: The results showed there was no effect of THI on milk production (p>0.05), despite having reached 76 THI score, instead NDF (p<0.05) and RR (p<0.001) affected milk production, it was not found effect of THI on RR (p>0.05), and NDF had trend (p<0.1). Limitations on study/implications: There were no limitations for this report. Findings/conclusions: According to the results obtained, THI threshold should be reconsidered according to the resistance of productively active cattle on dairy farms.  Objective: The aim of the present study was to evaluate the effect of the temperature-humidity index (THI), the content of neutral detergent fiber (NDF), and rumination rate (RR) on milk production in Holstein cows in a dairy farm located in Bajío de San José, Jalisco, Mexico. Design/methodology/approach: The THI is an indicator of the effect of the environmental climate can have on milk production, and likewise the nutritional content of forage is affected by weather conditions, such as the NDF is related with rumination activity of cows; increasing THI has shown a direct effect on milk production in cows. The HealthyCow 24 ® CSR remote equipment was used (SCR Engineers Ltd., Netanya, Israel), to monitor rumination, from a total registry of 284 cows with 2, 3, and 4 lactations distributed between August and December 2020 period, analyzing the NDF content from total mixed portion and monitoring the THI. Results: The results showed there was no effect of THI on milk production (p>0.05), despite having reached a THI score of 76, while NDF (p<0.05) and RR (p<0.001) affected milk production; an effect of THI on RR (p>0.05) was not found, and the NDF only had a trend (p<0.1). Limitations on study/implications: There were no limitations for the study. Findings/conclusions: According to the results obtained, the THI threshold should be reconsidered according to the resistance of the productively active cattle on dairy farms

Elaboración de fichas técnicas de dispositivos médicos en el marco de las evaluaciones de tecnologías sanitarias durante la pandemia por COVID-19: Una revisión de la situación a nivel mundial y reporte de la experiencia peruana

Background: Given the health emergency caused by COVID-19, the need for the use of medical devices was particularly relevant. Methodology: A non-systematic literature search was conducted to identify documents that address topics related to the development, implementation, evaluation and/or characteristics of technical datasheets for medical devices. In addition, the SAP System was reviewed for the collection and analysis of data related to pre-pandemic (2000-2019) and in-pandemic (2020-2021) procurement. Evidence: At the global level, the experiences of WHO, ECRI Institute and INAHTA were described. At the Latin American level, experiences were found in Ecuador, Colombia, Argentina, Brazil, Mexico and Panama. Finally, at the Peruvian level, the experience of EsSalud was reported, showing that, from March 6, 2020 to May 21, 2021, 47 technical specifications were prepared for medical devices, of which 41 had purchase records, and of these, 13 correspond to biomedical and complementary equipment. We prioritized the reporting of consumption information (expressed in quantities purchased) for three devices: compact pulse oximeter, high-flow oxygen therapy equipment and the oxygen concentrator (10 L/min). Conclusion: The preparation of technical sheets considers the best scientific evidence available, as well as the technical-technological aspects of the medical device. In EsSalud, its preparation has allowed the incorporation of a significant quantity and variety of biomedical equipment for the treatment of COVID-19, in addition they have been made available with recommendations for their clinical use based on the scientific evidence analyzed.Introducción: Ante la situación de emergencia sanitaria por la COVID-19, la necesidad de uso de dispositivos médicos tuvo especial relevancia. Metodología: Se realizó una búsqueda no sistemática de la literatura dirigida a la identificación de documentos que aborden tópicos relacionados al desarrollo, implementación, evaluación y/o características de fichas técnicas de dispositivos médicos. Así mismo, se revisó el Sistema SAP para la obtención y análisis de los datos relacionados a las compras antes de pandemia (2000-2019) y durante pandemia (2020-2021). Contenido: A nivel mundial, se describieron las experiencias de la OMS, Instituto ECRI e INAHTA. A nivel de Latinoamérica, se encontraron experiencias en Ecuador, Colombia, Argentina, Brasil, México y Panamá. Finalmente, a nivel Perú, se reportó la experiencia de EsSalud, evidenciándose que, del 6 de marzo de 2020 al 21 de mayo de 2021, se elaboraron 47 fichas técnicas de dispositivos médicos, de las cuales 41 figuraban con registros de compras, y de estos, 13 corresponden a equipos biomédicos y complementarios. Priorizamos el reporte de información del consumo (expresado en cantidades adquiridas) de tres dispositivos: pulsioxímetro compacto, equipo de oxigenoterapia de alto flujo y concentrador de oxígeno de 10 L/minuto. Conclusión: La elaboración de fichas técnicas considera la mejor evidencia científica disponible, así como los aspectos técnicos-tecnológicos propios del dispositivo médico. En EsSalud, su elaboración ha permitido incorporar una importante cantidad y variedad de equipos biomédicos para el tratamiento de COVID-19, ademas han sido puestos a disposición con recomendaciones de su uso clínico sustentadas en la evidencia científica analizada

Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells

The functional properties of circulating CD8+ T cells have been associated with immune control of HIV. However, viral replication occurs predominantly in secondary lymphoid tissues, such as lymph nodes (LNs). We used an integrated single-cell approach to characterize effective HIV-specific CD8+ T cell responses in the LNs of elite controllers (ECs), defined as individuals who suppress viral replication in the absence of antiretroviral therapy (ART). Higher frequencies of total memory and follicle-homing HIV-specific CD8+ T cells were detected in the LNs of ECs compared with the LNs of chronic progressors (CPs) who were not receiving ART. Moreover, HIV-specific CD8+ T cells potently suppressed viral replication without demonstrable cytolytic activity in the LNs of ECs, which harbored substantially lower amounts of CD4+ T cell–associated HIV DNA and RNA compared with the LNs of CPs. Single-cell RNA sequencing analyses further revealed a distinct transcriptional signature among HIV-specific CD8+ T cells from the LNs of ECs, typified by the down-regulation of inhibitory receptors and cytolytic molecules and the up-regulation of multiple cytokines, predicted secreted factors, and components of the protein translation machinery. Collectively, these results provide a mechanistic framework to expedite the identification of novel antiviral factors, highlighting a potential role for the localized deployment of noncytolytic functions as a determinant of immune efficacy against HIV

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a−/− mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling

Comportamiento hidroclimático de coníferas en el Cerro Potosí, Nuevo León, México

El Cerro Potosí (CPO) se caracteriza por un gradiente altitudinal de 2 200 a 3 719 m y por ser hábitat de diversas coníferas. Los objetivos de este estudio fueron: 1) generar una red dendrocronológica de Pinus culminicola, Pinus hartwegii, Pseudotsuga menziesii y Pinus greggii; 2) desarrollar una reconstrucción de lluvia estacional; y 3) determinar la influencia de fenómenos atmosféricos de circulación general sobre la variabilidad interanual y multianual de la precipitación en CPO. Para lograr esos objetivos, con métodos dendrocronológicos se generaron cuatro cronologías climáticamente sensitivas; la más extensa (1420-2010) fue de Pinus hartwegii, y las más corta (1850-2010), de Pinus greggii. La asociación entre series dendrocronológicas mostró una respuesta climática común y mediante componentes principales. Se integró una serie representativa de los diversos estratos de elevación, que cubre el período 1700-2010. La reconstrucción de lluvia estacional enero-septiembre detectó que los años más secos fueron 1785 y 1801, y los más húmedos, 1791, 1832 y 1911, con una influencia significativa (r= 0.53, p<0.01) del Niño Oscilación del Sur (ENSO), a través del índice de lluvia tropical (TRI). La influencia de huracanes detectada en las series de madera tardía constituye una alternativa para analizar, históricamente, la influencia de estos fenómenos atmosféricos en el crecimiento de las especies y en la producción de servicios hidrológicos para la región

Memoria del I Coloquio de verano de investigación de la Escuela de Negocios de ITESO, 2022

Esta memoria recoge cinco de las ponencias presentadas en el Coloquio de investigación de verano de la ENI, 2022. Son una muestra del trabajo de investigación que hacemos en el Departamento de Economía, Administración y Mercadología (DEAM), en el Centro Universidad Empresa (CUE) y en el Centro para la Gestión de la Innovación y la Tecnología (CEGINT); una investigación con una orientación principalmente práctica y aplicada, enfocada a las micro, pequeñas y medianas empresas y a su contexto socioeconómico. Esperamos que puedan ser ocasión de diálogo y de contribución no sólo al campo académico en el que nos desenvolvemos, sino también a las realidades mismas en las que queremos colaborar para apoyar los esfuerzos hacia una economía y una sociedad más justas y más humanas.ITESO, A.C

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum